A List of FDA 483 Observations in FY 2022
1. The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed].
2. There is a failure to thoroughly review [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] whether or not the batch has been already distributed.
3. Your firm failed to establish [adequate] written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or represented to possess.
4. Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity.
5. Equipment used in the manufacture, processing, packing or holding of drug products is not [of appropriate design] [of adequate size] [suitably located] to facilitate operations for its [intended use] [cleaning and maintenance].
6. Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel.
7. Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product.
8. Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the [final specifications] [identity and strength of each active ingredient] prior to release.
9. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed].
10. Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product.
11. Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance.
12. Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.
13. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include [adequate] validation of the [aseptic] [sterilization] process.
14. Control procedures are not established which [monitor the output] [validate the performance] of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.
15. There is no written testing program designed to assess the stability characteristics of drug products.
16. Written records of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications] do not [always] include the conclusions and follow-up.
17. Written production and process control procedures are not [followed in the execution of production and process control functions] [documented at the time of performance].
18. Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the [room] [equipment] to produce aseptic conditions.
19. Employees are not given training in [the particular operations they perform as part of their function] [current good manufacturing practices] [written procedures required by current good manufacturing practice regulations].
20. Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing.
21. The [accuracy] [sensitivity] [specificity] [reproducibility] of test methods have not been [established] [documented].
22. Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not [established] [written] [followed].
23. Batch production and control records [are not prepared for each batch of drug product produced] [do not include complete information relating to the production and control of each batch].
24. There is no quality control unit.
25. The written stability testing program is not followed.
26. Buildings used in the [manufacturing] [processing] [packing] [holding] of a drug product are not maintained in a good state of repair.
27. Written records are not [always] made of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications].
28. Procedures describing the handling of written and oral complaints related to drug products are [not written or followed] [deficiently written or followed].
29. Buildings used in the manufacture, processing, packing or holding of drug products are not [maintained in a clean and sanitary condition] [free of infestation by rodents, birds insects, and other vermin].
30. Established [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] are not [followed] [documented at the time of performance].
31. Equipment for adequate control over [air pressure] [micro-organisms] [dust] [humidity] [temperature] is not provided when appropriate for the manufacture, processing, packing or holding of a drug product.
32. Deviations from written production and process control procedures are not [recorded] [justified].
33. Drug products are not stored under appropriate conditions of [temperature] [humidity] [light] so that their identity, strength, quality, and purity are not affected.
34. The quality control unit lacks authority to [review production records to assure that no errors have occurred] [fully investigate errors that have occurred].
35. Strict control is not exercised over labeling issued for use in drug product labeling operations.
36. Establishment of the reliability of the component supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals.
37. Records are not maintained so that data therein can be reviewed at least annually to evaluate the quality standards of each drug product to determine the need for changes in specifications or manufacturing or control procedures.
38. Investigations of [an unexplained discrepancy] [a failure of a batch or any of its components to meet any of its specifications] did not extend to [other batches of the same drug product] [other drug products that may have been associated with the specific failure or discrepancy].
39. The batch production and control records are deficient in that they do not include documentation of the accomplishment of each significant step in [manufacturing] [processing] [packing] [holding].
40. Input to and output from [the computer] [related systems of formulas] [records or data] are not checked for accuracy.
41. Reserve samples from representative sample lots or batches of drug products selected by acceptable statistical procedures are not examined visually at least once a year for evidence of deterioration.
42. Reports of analysis from component suppliers are accepted in lieu of testing each component for conformity with all appropriate written specifications, without [performing at least one specific identity test on each component] [establishing the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals].
43. Employees engaged in the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] required to perform their assigned functions.
44. Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable [size] [construction] [location] to facilitate cleaning, maintenance, and proper operations.
45. Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.
46. Records are not kept for the [maintenance] [cleaning] [sanitizing] [inspection] of equipment.
47. The written stability program for drug products does not include [reliable] [meaningful] [specific] test methods.
48. An adequate number of batches of each drug product are not tested [nor are records of such data maintained] to determine an appropriate expiration date.
49. Procedures for the cleaning and maintenance of equipment are deficient regarding sufficient detail of the methods, equipment, and materials used in the cleaning and maintenance operation, and the methods of disassembly and reassembling equipment as necessary to assure proper cleaning and maintenance.
50. Aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure.
51. Specific identification tests are not conducted on components that have been accepted based on the supplier's report of analysis.
52. Written procedures for cleaning and maintenance fail to include [assignment of responsibility] [maintenance and cleaning schedules] [description in sufficient detail of methods, equipment and materials used] [description in sufficient detail of the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance] [instructions for removal or obliteration of previous batch identification] [instructions for protection of clean equipment from contamination prior to use] [parameters relevant to the operation].
53. The calibration of [instruments] [apparatus] [gauges] [recording devices] is not done at suitable intervals [in accordance with an established written program] [with provisions for remedial action in the event accuracy and/or precision limits are not met].
54. The quality control unit lacks responsibility to [approve] [reject] all procedures or specifications impacting on the [identity] [strength] [quality] [purity] of drug products.
55. Written procedures are not [established] [followed] for evaluations conducted at least annually to review records associated with a representative number of batches, whether approved or rejected.
56. Written records of major equipment [cleaning] [maintenance] [use] are not included in individual equipment logs.
57. Written procedures are not [established] [followed] for evaluations done at least annually and including provisions for a review of [complaints] [recalls] [returned or salvaged drug products] [investigations conducted for each drug product].
58. Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product.
59. Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time of use.
60. Written procedures are lacking which describe in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].
61. The establishment of [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] including any changes thereto, are not [drafted by the appropriate organizational unit] [reviewed and approved by the quality control unit].
62. The identity of each component of a drug product is not verified by conducting at least one test to verify the identity, using specific identity tests if they exist.
63. Procedures describing the handling of all written and oral complaints regarding a drug product are not [established] [written] [followed].
64. You produced hazardous drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.
65. The quality control unit lacks the responsibility and authority to [approve] [reject] all [components] [drug product containers] [closures] [in process materials] [packaging material] [labeling] [drug products].
66. GMP training is not conducted [on a continuing basis] [with sufficient frequency] to assure that employees remain familiar with CGMP requirements applicable to them.
67. Failure to maintain a backup file of data entered into the computer or related system.
68. Actual yield and percentages of theoretical yield are not determined at the conclusion of each appropriate phase of [manufacturing] [processing] [packaging] [holding] of the drug product.
69. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products.
70. Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.
71. Laboratory records are deficient in that they do not include a complete record of all data obtained during testing.
72. Complaint records are deficient in that they do not include the findings of the [investigation] [follow-up].
73. Written procedures are not [established] [followed] that describe the [in-process controls] [tests] [examinations] to be conducted on appropriate samples of in-process materials of each batch.
74. Written procedures are not followed for the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].
75. The labels of your outsourcing facility's drug products are deficient.
76. Access to the storage area for labels and labeling materials is not limited to authorized personnel.
77. Procedures designed to assure that correct [labels] [labeling] [packaging materials] are used for drug products are not [written] [followed].
78. There was a failure to handle and store [components] [drug product containers] [closures] at all times in a manner to prevent contamination.
79. Each lot of [components] [drug product containers] [closures] is not withheld from use until the lot has been sampled, tested, examined, and released by the quality control unit.
80. Written procedures are not [drafted, reviewed and approved by the appropriate organizational units] [reviewed and approved by the quality control unit].
81. Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit].
82. Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for drug products.
83. Results of stability testing are not used in determining [appropriate storage conditions] [expiration dates].
84. Master production and control records lack [complete manufacturing and control instructions] [sampling and testing procedures] [specifications] [special notations] [precautions to be followed].
85. Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of post marketing adverse drug experiences.
86. Non-microbial contamination was observed in your production area.
87. The [separate or defined areas] [control systems] necessary to prevent contamination or mix-ups are deficient.
88. Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use.
89. Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed.
90. Drug product production and control records, are not [reviewed] [approved] by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed.
91. The master production and control records are deficient in that they do not include complete [manufacturing] [control] [instructions] [sampling] [testing] [procedures] [specifications] [special notations] [precautions].
92. Deviations from written [specifications] [standards] [sampling plans] [test procedures] [laboratory mechanisms] are not [recorded] [justified].
93. Procedures describing the calibration of instruments, apparatus, gauges and recording devices are [not written or followed] [deficiently written or followed].
94. Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.
95. An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning a failure of one or more distributed batches of a drug to meet the specifications established for it in the application.
96. The ISO 5 classified aseptic processing areas had [difficult to clean] [particle-generating] [visibly dirty] equipment or surface.
97. You used a non-pharmaceutical grade component in the formulation of a drug product.
98. The quality control unit lacks responsibility for approving or rejecting drug products [manufactured] [processed] [packed] [held] under contract by another company.
99. Protective apparel is not worn as necessary to protect drug products from contamination.
100. Drug product [containers] [closures] were not [clean] [sterilized and processed to remove pyrogenic properties] to assure that they are suitable for their intended use.
101. All records of [production] [control] [distribution] [components] [drug product containers] [closures] [labeling] associated with a batch of drug product were not maintained at least one (1) year after the expiration date.
102. Drug products failing to meet established [standards] [specifications] [quality control criteria] are not rejected.
103. The written stability program for drug products does not describe the storage conditions for samples retained for testing.
104. Accelerated stability studies, combined with basic stability information, used to support tentative expiration dates are not supported with ongoing full shelf life studies.
105. The batch production and control records are deficient in that they are not [an accurate reproduction of the appropriate master production or control record] [checked for accuracy, dated, and signed].
106. Verification of the suitability of the testing methods is deficient in that they are not [performed under actual conditions of use] [documented on the laboratory records].
107. There is a lack of written procedures [assigning responsibility] [providing cleaning schedules] [describing in sufficient detail the methods, equipment and materials to be used] for sanitation.
108. In-process materials are not tested for [identity] [strength] [quality] [purity] and approved or rejected by the quality control unit [during the production process] [after storage for long periods].
109. Backup data is not assured as [exact] [complete] [secure from alteration, erasure or loss] through keeping hard copy or alternate systems.
110. Laboratory records do not include the initials or signature of a second person showing that the original records have been reviewed for [accuracy] [completeness] [compliance with established standards].
111. An annual report was not submitted [each year] [within 60 days of the anniversary date of U.S. approval of the application] to the FDA division responsible for reviewing the application.
112. You did not [establish] [follow] written quality assurance procedures.
113. [Equipment was] [Materials or supplies were] not disinfected prior to entering the aseptic processing areas.
114. Your facilities are not adequate to ensure [the orderly handling of materials and equipment] [the prevention of mix-ups] [the prevention of contamination of equipment or product by substances, personnel, or environmental conditions] that could reasonably be expected to have an adverse effect on product quality.
115. Your outsourcing facility did not submit a report to FDA identifying the drugs compounded during the previous six month period.
116. The number of qualified personnel is inadequate to [perform] [supervise] the [manufacture] [processing] [packing] [holding] of each drug product.
117. The flow of [components] [drug product containers] [closures] [labeling] [in-process materials] [drug products] through the building is not designed to prevent contamination.
118. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the holding of rejected [components] [drug product containers] [closures] [labeling] before disposition.
119. The batch records do not record the distinctive [identification number] [code] [name of equipment] to identify major equipment to show the specific equipment used in the manufacture of a batch of a drug product.
120. Procedures prescribing a system for reprocessing batches to insure that the reprocessed batches will conform with all established standards, specifications, and characteristics are not [written] [followed].
121. The drug product is not identified with a lot or control number that permits the determination of the history of the manufacture and control of the batch.
122. The [number of containers to be sampled] [amount of material taken from each container] is not based upon appropriate criteria.
123. Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.
124. Container closure systems do not provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product.
125. The written stability program for drug products does not include [sample size] [test intervals] based on statistical criteria for each attribute examined to assure valid estimates of stability.
126. Test procedures relative to appropriate laboratory testing for [sterility] [pyrogens] are not [written] [followed].
127. Individual equipment logs do not show [time] [date] [product] [lot number of each batch processed].
128. The master production and control records for each batch size of drug product are not [prepared, dated, and signed by one person with a full handwritten signature] [independently checked, dated, and signed by a second person].
129. Procedures for the preparation of master production and control records are not [described in a written procedure] [followed].
130. Distribution records do not contain the [name and strength of the drug product] [description of dosage form] [name and address of consignee] [date and quantity shipped] [lot or control number of drug product].
131. The plumbing system contains defects that could contribute to the contamination of drug products.
132. Written procedures are lacking for the use of [rodenticides] [insecticides] [fungicides] [fumigating agents] [cleaning and sanitizing agents] designed to prevent the contamination of [equipment] [components] [drug product containers] [closures] [packaging, labeling materials] [drug products].
133. Acceptance criteria for the sampling and testing conducted by the quality control unit is not adequate to assure that batches of drug products meet [each appropriate specification] [appropriate statistical quality control criteria] as a condition for their approval and release.
134. A written record of the program along with appropriate validation data has not been maintained in situations where backup data is eliminated by computerization or other automated processes.
135. Batch production and control records do not include complete labeling control records, including specimens or copies of all labeling used for each batch of drug product produced.
136. Written records of investigation of a drug complaint do not include [the findings of the investigation] [the follow-up].
137. Master production and control records lack a statement of theoretical yield [including the maximum and minimum percentages of theoretical yield beyond which investigation is required].
138. The suitability of all testing methods is not verified under actual conditions of use.
139. The container labels of your outsourcing facility's drug products are deficient.
140. Vermin was observed in your production area.
141. You had inadequate HEPA filter [coverage] [airflow] over the area to which sterile product was exposed.
142. The preparation of your master production and control records was not [described in a written procedure] [followed in accordance with your written procedure].
143. You did not [implement procedures] [document your activities in accordance with your procedures] to ensure that all equipment is [cleaned] [suitable for its intended purposes] [properly installed, maintained, and capable of repeatedly producing valid results] that could reasonably be expected to adversely affect the identity, strength, quality, or purity of a PET drug, or give erroneous or invalid test results when improperly used or maintained.
144. Individuals responsible for supervising the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] to perform their assigned functions in such a manner as to assure the drug product has the safety, identity, strength, quality and purity that it purports or is represented to possess.
145. Clothing of personnel engaged in the [manufacturing] [processing] [packing] [holding] of drug products is not appropriate for the duties they perform.
146. Procedures for the cleaning and maintenance of equipment are deficient regarding maintenance and cleaning schedules, including, where appropriate, sanitizing schedules.
147. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the receipt, identification, storage, and withholding from use of [components] [drug product containers] [closures] [labeling] pending sampling, testing, or examination by the quality control unit before release for manufacturing or packaging.
148. Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations.
149. Discrepancies found outside preset limits when reconciling the quantities of labeling issued, used and returned, were not [evaluated] [investigated].
150. Inspection of the [packaging] [labeling] facilities immediately before use is not done to assure that all drug products have been removed from previous operations.
151. Inspection of the [packaging] [labeling] facilities is not done after use to assure that materials not suitable for subsequent operations have been removed.
152. Drug product expiration dates do not appear on the labeling in the manner prescribed by regulations.
153. The distribution system is deficient in that each lot of drug product cannot be readily determined to facilitate its recall if necessary.
154. Representative samples are not taken of each shipment of each lot of [components] [drug product containers] [closures] for testing or examination.
155. Records associated with drug product [components] [containers] [closures] [labeling] [production] [control] [distribution] and within the retention period for such records, were not made readily available for authorized inspection.
156. The written stability program does not assure testing of the drug product in the same container-closure system as that in which the drug product is marketed.
157. The procedures for the annual quality standards record evaluation are deficient in that they do not address a review of a representative number of [approved] [rejected] batches.
158. The persons [performing] [double-checking] the cleaning and maintenance are not [dating] [signing or initialing] the equipment cleaning and use log.
159. There is no documentation of the examination and review of labels and labeling for conformity with [established specifications] [the assigning of a lot or control number].
160. The batch production and control records are deficient in that they do not include the identity of major [equipment] [lines] used.
161. The batch production and control records are deficient in that they do not include identification of persons [performing] [supervising] [checking] each significant step in the operation.
162. Laboratory records are deficient in that they do not include a statement of the results of tests and how they compare to the established [specifications] [standards].
163. Laboratory records are deficient in that they do not include the [initials] [signature] of the second person reviewing the record for accuracy.
164. Complaint records are deficient in that they do not include the known [name and strength of the drug product] [lot number] [name of complainant] [nature of complaint] [reply to complainant].
165. Drains are not [of adequate size] [provided with an air break or other mechanical device to prevent back-siphonage where connected directly with a sewer].
166. Washing and toilet facilities lack [hot and cold water] [soap or detergent] [air driers or single-service towels] [cleanliness].
167. All [compounding and storage containers] [processing lines] [major equipment] used during the production of a batch of drug product is not properly identified at all times to indicate [contents] [the phase of processing of the batch].
168. Rejected in-process materials are not [identified] [controlled under a quarantine system] to prevent their use in manufacturing or processing operations for which they are unsuitable.
169. In-process samples are not [representative] [properly identified].
170. Written calibration procedures for instruments, apparatus, gauges, and recording devices are deficient in that they do not include specific [directions] [schedules] [limits for accuracy and precision] [provisions for remedial action if limits are not met].
171. Certificates of testing of [containers] [closures] are accepted in lieu of testing without [a visual identification] [establishing the reliability of the supplier's test results through appropriate validation of the test results at appropriate intervals].
172. Each lot of a [component] [drug product container] [closure] that is liable to microbiological contamination that is objectionable in view of its intended use is not subjected to microbiological tests before use.
173. Each container of component dispensed to manufacturing is not examined by a second person to assure that [the component was released by the quality control unit] [the weight or measure is correct as stated in the batch records] [the containers are properly identified].
174. Results of inspection of packaging and labeling facilities are not documented in the batch production records.
175. A system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary, has not been established.
176. The use of [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications was observed.
177. Non-penicillin drug products were not tested for the presence of penicillin, when a reasonable possibility existed that a non-penicillin drug product has been exposed to a cross-contamination with penicillin.
178. Written procedures describing the handling of complaints do not include provisions for [review by the quality control unit of any complaint involving the possible failure of a drug product to meet any of its specifications] [a determination as to the need for an investigation of any unexplained discrepancy] [explaining the reasons for the failure of the batch or any of its components to meet specifications].
179. Laboratory records do not include [a description of the sample received for testing] [the source or location from where the sample was obtained] [the quantity of the sample] [the lot number or other distinctive code of the sample] [the date the sample was taken] [the date the sample was received for testing].
180. Not all quarterly periodic adverse drug experience reports have been submitted within 30 days of the close of the quarter.
181. Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application.
182. Your firm lacks adequate production and process controls to ensure the consistent production of a PET drug that meets the applicable standards of identity, strength, quality and purity.
183. You produced beta-lactam drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.
184. Personnel did not [disinfect] [change gloves frequently enough] to prevent contamination.
185. Personnel engaged in aseptic processing were observed with [exposed hands] [exposed wrists] [exposed legs] [exposed hair] [exposed mouth].
186. Personnel moved rapidly in the vicinity of [open sterile units] [instruments], which disrupted the airflow and increased the risk of bringing lesser quality air into the ISO 5 classified aseptic processing area.
187. Personnel [conducted aseptic manipulations] [placed equipment/supplies] in an area that blocked the movement of first pass air around an open unit, either before or after it was filled with sterile product.
188. You did not make adequate product evaluation and take remedial action where actionable microbial contamination was found to be present in the ISO 5 classified aseptic processing area during aseptic production.
189. You did not make adequate product evaluation and take remedial action where actionable microbial contamination was found to be present in an area adjacent to the ISO 5 classified aseptic processing area during aseptic production.
190. Your facility design allowed the influx of poor quality air into a higher classified area.
191. The filter intended to render final product sterile [was not adequate to accomplish sterilization] [was not pharmaceutical grade].
192. Disinfectant contact time (also known as "dwell time") and coverage of the item being disinfected were insufficient to achieve adequate levels of disinfection.
193. Your examination and testing of samples did not assure that the drug product and in-process material conformed to specifications.
194. Production personnel were not practicing good sanitation and health habits.
195. Substances required for equipment operations such as lubricants and coolants come in contact with [components] [drug product containers] [closures] [in-process materials] [drug product] so as to alter the safety, identity, strength, quality or purity of the drug product beyond the official or other established requirements.
196. Procedures for the cleaning and maintenance of equipment are deficient regarding assignment of responsibility for cleaning and maintaining equipment.
197. Records of the [calibration checks] [inspections] of automatic, mechanical or electronic equipment, including computers or related systems are not maintained.
198. Written production and control procedures include batches formulated with the intent to provide less than 100 percent of the labeled or established amount of active ingredient.
199. Each component is not added to a batch by one person and verified by a second person.
200. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of in-process materials.
201. Separate or defined areas to prevent contamination or mix-ups are deficient regarding the packaging and labeling operations.
202. Aseptic processing areas are deficient in that [floors] [walls] [ceilings] are not smooth and/or hard surfaces that are easily cleanable.
203. Obsolete or outdated labels, labeling and packaging materials are not destroyed.
204. Excess labeling bearing lot or control numbers is not destroyed.
205. There is insufficient physical or spatial separation from operations and other drug products to prevent mix-ups and cross-contamination.
206. Examination of packaging and labeling materials for suitability and correctness before packaging operations is [not performed] [not documented in the batch production records].
207. Samples of representative units were not [collected] [visually examined] for correct labeling at the completion of finishing operations.
208. Approved [components] [drug product containers] [closures] are not retested or reexamined as appropriate for identity, strength, quality and purity after [storage for long periods] [exposure to conditions that might have an adverse effect] with subsequent approval or rejection by the quality control unit.
209. Each container or grouping of containers of [components] [drug product containers] [closures] is not examined visually upon receipt and before acceptance for [appropriate labeling as to contents] [container damage] [broken seals] [contamination].
210. Incoming [components] [drug product containers] [closures] are not stored under quarantine until they have been tested or examined, as appropriate, and released.
211. Sampling procedures are deficient regarding sampling components from the top, middle, and bottom of container.
212. Establishment of the reliability of the [container] [closure] supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals.
213. Failure to reject any lot of [components] [drug product containers] [closures] that did not meet the appropriate written specifications for identity, strength, quality, and purity.
214. Drug product containers or closures are [reactive] [additive] [absorptive] so as to alter the safety, identity, strength, quality, and purity of the drug beyond the official or established requirements.
215. Records for all [production] [control] [distribution] [components] [drug product containers] [closures] [labeling] associated with a batch of OTC drug product exempt from expiration dating were not maintained for 3 years after distribution of the last lot of drug product incorporating the component or using the container, closure, or labeling.
216. Sampling and testing plans for drug products are not described in written procedures which include the [method of sampling] [number of units per batch to be tested].
217. There is no written assessment of stability of homeopathic drug products based at least on [testing or examination of the drug product for compatibility of the ingredients] [marketing experience with the drug product to indicate that there is no degradation of the product for the normal or expected period of use].
218. Each batch of drug product purporting to be [sterile] [pyrogen-free] is not laboratory tested to determine conformance to such requirements.
219. The batch production and control records are deficient in that they do not include specific identification of each [batch of component] [in-process material] used.
220. The batch production and control records are deficient in that they do not include [complete labeling control records] [specimen] [copy] of labeling.
221. The batch production and control records are deficient in that they do not include documentation of sampling performed.
222. Laboratory records do not include complete records of any testing and standardization of laboratory [reference standards] [reagents] [standard solutions].
223. Laboratory records do not include complete records of the periodic calibration of laboratory [instruments] [apparatus] [gauges] [recording devices].
224. Laboratory records do not include complete records of all stability testing performed.
225. Animals used in the testing of [component] [in-process materials] [drug products] are not maintained and controlled in a manner that assures their suitability for their intended use.
226. The master production and control records are deficient in that they do not include a statement of theoretical yield and [minimum] [maximum] [yield percentages].
227. Laboratory records are deficient in that they do not include a statement of the [weight] [measure] of the sample used for testing.
228. Equipment surfaces that contact [components] [in-process materials] [drug products] are reactive, additive or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.
229. Adequate ventilation is not provided.
230. Air-handling systems for the [manufacture] [processing] [packing] of penicillin are not completely separate from those for other drug products for human use.
231. The potable water being permitted for use in the potable water system fails to meet standards prescribed by the Environmental Protection Agency.
232. Containers holding subdivided components for drug product manufacturing are deficiently identified in that they lack the [component name] [item code].
233. Determinations of conformance to appropriate written specifications for acceptance are deficient in that they are not made for each lot within each shipment of [components] [drug product containers] [closures] [labeling] used in the manufacture, processing, packing or holding of drug products.
234. Drug product samples are not [representative of the entire batch] [properly identified].
235. Test devices are deficient in that [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications are used.
236. Reserve drug product samples are not [appropriately identified] [representative of each lot or batch of drug product] [retained and stored under conditions consistent with product labeling].
237. Drug product reserve samples are not stored in [the same immediate container-closure system as the marketed product] [an immediate container-closure system that has essentially the same characteristics as the marketed product].
238. Evidence of reserve drug product sample deterioration was not [investigated] [recorded and maintained with other stability data].
239. Written procedures for sanitation are not followed.
240. Containers from which samples have been taken are not marked to show that samples have been taken from them.
241. For components removed from the original containers, the new container fails to be identified with [component name or item code] [receiving or control number] [weight or measure] [batch for which component was dispensed including product name, strength and lot number].
242. Reprocessing procedures lack the steps to be taken to insure that reprocessed batches will conform with all established standards, specifications, and characteristics.
243. Examination and testing of samples is not done to assure that in-process materials conform to specifications.
244. Procedures describing the warehousing of drug products are not [established] [followed].
245. Laboratory controls do not include determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] used in the manufacture, processing, packing, or holding of drug products.
246. Laboratory controls do not include a determination of conformance to [written descriptions of sampling procedures] [appropriate specifications] for drug products.
247. The statistical quality control criteria fail to include appropriate [acceptance levels] [rejection levels].
248. Written procedures for sampling and testing plans are not followed for each drug product.
249. Batch production and control records for each batch of drug product produced do not include an accurate reproduction of the appropriate master production or control record which was checked for accuracy, dated and signed.
250. Batch production and control records do not include the identification of the persons [performing] [directly supervising] [checking] each significant step in the operation, for each batch of drug product produced.
251. Batch production and control records do not include the weights and measures of components used in the course of processing each batch of drug product produced.
252. Batch production and control records do not include the specific identification of each batch of [component] [in-process material] used for each batch of drug product produced.
253. Batch production and control records do not include dates of each significant step in the [manufacture] [processing] [packing] [holding] of the batch for each batch of drug product produced.
254. The written record or copy of the record of an investigation of a complaint conducted in relation to [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] is not maintained at the establishment where the investigation occurred.
255. A written record of each complaint is not maintained in a file designated for drug product complaints [at the facility where the drug product was manufactured, processed or packed] [at a facility other than the facility in which the drug product was manufactured, processed or packed provided the written records are readily available for inspection at that other facility].
256. The master production and control records lack an accurate statement of the [weight] [measure] of each component [using the same weight system for each component].
257. Master production and control records lack [a description of the drug product containers, closures and packaging materials] [a specimen or copy of each label and all other labeling] [the signatures and dates entered by the person or persons responsible for the approval of labeling].
258. Laboratory records do not include a record of all calculations performed in connection with the test.
259. Laboratory records do not include [the initials or signature of the person who performs each test] [the date(s) the tests were performed].
260. The building lacks adequate space for the orderly placement of equipment and materials to prevent mix-ups between [different components] [drug product containers] [closures] [labeling] [in-process materials] [drug products] and to prevent contamination.
261. Adverse drug experience information has not been reported to FDA.
262. Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of initial receipt of the information.
263. Adverse drug experiences that were the subject of post marketing 15-day reports were not [promptly] investigated.
264. Periodic reports of non-alert adverse drug experiences have not been submitted [quarterly for an application which was approved less than three years ago] [yearly for an application which was approved three or more years ago].
265. You failed to maintain for a period of 10 years records of all adverse drug experiences known to you, including raw data and any correspondence.
266. An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning [bacteriological contamination] [significant chemical, physical, or other change or deterioration] in a distributed drug product.
267. You did not approve or reject, before implementation, [any initial] [any proposed changes to existing] [specifications] [methods] [processes or procedures] to ensure that they maintain the identity, strength, quality, and purity of a PET drug.
268. When errors occurred or a production batch or any component of the batch, failed to meet specifications, you did not [determine the need for an investigation] [conduct an investigation] [take appropriate corrective actions] when necessary.
269. Each lot of [components] [containers] [closures] is not [uniquely identified] [tested or examined to determine compliance with your specifications].
270. You failed to submit an ICSR for the reporting period [within 30 days of the close of the quarter] [within 60 days of the anniversary date of the approval of the application].
271. You submitted an ICSR reporting initial reporter information that failed to include the [name] [address] [telephone number] [whether initial reporter is health care professional] [occupation of health care professional].
272. Vermin was observed in an area immediately adjacent to your production area.
273. You produced highly potent drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.
274. Personnel engaged in aseptic processing were observed wearing non-sterile gloves.
275. Personnel touched equipment or other surfaces located outside of the ISO 5 classified aseptic processing area with gloved hands and then engaged in aseptic processing without changing or sanitizing gloves.
276. The [ISO 5 classified aseptic processing areas] [segregated production areas surrounding the ISO 5 classified aseptic processing area] contained dust-collecting overhangs without adequate and frequent cleaning.
277. The ISO 5 classified aseptic processing area was located within a non-classified room (segregated production area).
278. [Non-sterilized] [Non-depyrogenated] equipment was used in sterile drug production.
279. Sporicidal agents were not used in your facility's cleanrooms and/or ISO 5 classified aseptic processing area.
280. The use of sporicidal agents in the [cleanrooms] [ISO 5 classified aseptic processing] area was [inadequate] [infrequent].
281. An application holder did not dispense the Medication Guide, as required by your approved REMS Medication Guide.
282. You did not [distribute the Communication Plan in accordance with the distribution dates in the REMS] [distribute the Communication Plan to the targeted audience described in the REMS] [use the Communication Plan distribution methods described in the REMS], as required by your approved REMS Communication Plan.
283. An application holder did not [ensure wholesalers / distributors who distribute the drug are authorized to distribute the drug] [comply with the audit plan and schedule described in the REMS] [identify and address non-compliant authorized wholesalers / distributors] [maintain a Support / Call Center or a REMS Program website] [maintain the drug distribution and dispensing records to ensure restricted distribution], as required by your approved REMS Implementation System.
Read also: FDA Inspection Database